Feline immunodeficiency virus (FIV) is a lentivirus analogous to HIV in that it targets T lymphocytes via mucosal and vertical pathways, causes fatal immunodeficiency, and has emerged relatively recently in its host species, the domestic cat (Felis domestica). In contrast, the FIV-like lentiviruses of non-domestic felids, including the puma (cougar mountain lion, Felis concolor), have apparently been present in their host populations for long periods of time, leading to lentiviral/host adaptation--analogous to simian immunodeficiency virus (SIV) in African non-human primate hosts. In preliminary studies we have found that domestic cats infected with puma lentivirus (PLV) do not experience clinical disease, develop a strong anti-lentiviral immune response, and are partially protected against subsequent challenge with virulent FIV in the absence of clinical disease. Other preliminary data in a cohort of cougars naturally infected with PLV suggests that purifying selection, i.e., selection dependent upon viral fitness rather than host immune response may be an additional or secondary vital force shaping evolution of the PLV population. We will therefore assess both the immune response and the viral evolutionary selection during infections by the newly emergent FIV vs. the more ancient PLV in their adapted and non-adapted feline hosts. These studies will provide insight into the mechanisms whereby the host downregulates and/or the virus selects virulent versus attenuated species--questions pertinent to the pathogenesis, adaptation, and control of HIV infection and AIDS.